A traditional Chinese medicine composition for treating adenomyosis and application thereof

Abstract

The application belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating adenomyosis and application thereof. The traditional Chinese medicine composition is prepared from raw medicinal materials in the following mass fractions: 20-45 parts of Astragalus membranaceus, 10-15 parts of Ramulus Cinnamomi, 10-15 parts of Angelica sinensis, 10-15 parts of Fried Semen Persicae, 6-9 parts of Rhei Radix et Rhizoma with liquor, 10-12 parts of Poria cocos, 6-9 parts of Eupolyphaga, 6-9 parts of Yunnan giant Himalayan lily, and 3-6 parts of Panax notoginseng powder. The clinical research results prove that the traditional Chinese medicine composition can effectively treat adenomyosis of yang deficiency and blood stasis type, improve symptoms such as dysmenorrhea, chronic pelvic pain, menorrhagia, prolonged menstrual period and the like of patients, and improve hemoglobin level, while avoiding obvious adverse reactions, and therefore has good practical application value.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for treating adenomyosis and its application. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Adenomyosis (AM) is a group of estrogen-dependent diseases in which active endometrial tissue (glandules and stroma) appears in the myometrium. Clinically, it often manifests as progressively worsening dysmenorrhea, menorrhagia, and secondary infertility.

[0004] In recent years, the incidence of adenomyosis has ranged from 5% to 70%, and is increasing year by year, showing a trend towards affecting younger women. Among them, up to 48% of patients experience progressively worsening dysmenorrhea (which can lead to fainting in severe cases), and about 40-50% of patients experience menorrhagia and prolonged menstrual periods (even leading to severe anemia). At the same time, adenomyosis has been found in 34.3% of infertile patients. It is a common and difficult gynecological disease that seriously affects women's physical and mental health and quality of life.

[0005] There is no standardized treatment for adenomyosis (AM). Western medicine primarily employs drug therapy and surgery. Drug therapy often includes nonsteroidal anti-inflammatory drugs (NSAIDs), high-potency progestins, oral contraceptives, androgen derivatives, and gonadotropin-releasing hormone analogs. However, these treatments have high relapse rates after discontinuation and can cause side effects such as abnormal vaginal spotting. Surgical treatment significantly impairs and deprives women of their reproductive function, resulting in low clinical acceptance. In contrast, traditional Chinese medicine (TCM) demonstrates significant efficacy in controlling adenomyosis pain, improving fertility, and managing the disease long-term, with high safety profiles and unique advantages.

[0006] There are currently reports on traditional Chinese medicines for the treatment of adenomyosis, with some targeting the excess syndrome type of adenomyosis, and some for the treatment of the deficiency syndrome type of adenomyosis and endometriosis. The inventor has been engaged in the clinical and research work of traditional Chinese medicine gynecology for a long time and has summarized the yang deficiency and blood stasis syndrome type with intermingled excess and deficiency in adenomyosis. The inventor once invented the traditional Chinese medicine "Tongmai Huazheng Mixture" for the treatment of adenomyosis, which is composed of Chinese cinnamon twig, angelica sinensis, astragalus membranaceus, poria cocos, ligusticum wallichii, red peony root, moutan bark, stir-fried peach kernels, ground beetle, rheum officinale, paris polyphylla, oldenlandia diffusa, Chinese dates, ginger, honey and other drugs, and has the effects of "warming yang and supplementing qi, promoting blood circulation and resolving stasis". Tongmai Huazheng Mixture is a traditional Chinese medicine medical institution preparation of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine and is clinically used for the treatment of adenomyosis with yang deficiency and blood stasis syndrome. Through clinical observation and research, after using "Tongmai Huazheng Mixture" for about 3 menstrual cycles, dysmenorrhea and chronic pelvic pain and other symptoms have been significantly improved. However, the effective rate of this formula is not enough to meet the clinical needs, and its effect on menorrhagia and prolonged menstrual period caused by adenomyosis is not clear. Summary of the Invention

[0007] Aiming at the deficiencies of the above-mentioned existing technologies, the purpose of the present invention is to provide a traditional Chinese medicine composition for the treatment of adenomyosis and its application. The clinical research results prove that the traditional Chinese medicine composition of the present invention can effectively treat adenomyosis with yang deficiency and blood stasis type, improve symptoms such as dysmenorrhea, chronic pelvic pain, menorrhagia, and prolonged menstrual period of patients, increase the hemoglobin level, and avoid obvious adverse reactions at the same time. Based on the above research results, the present invention is thus completed.

[0008] To achieve the above purpose, the present invention adopts the following technical solutions: In the first aspect of the present invention, there is provided a traditional Chinese medicine composition for the treatment of adenomyosis, which is made from the following raw materials in parts by mass: Astragalus membranaceus 20 - 45 parts, Chinese cinnamon twig 10 - 15 parts, angelica sinensis 10 - 15 parts, stir-fried peach kernels 10 - 15 parts, rheum officinale 6 - 9 parts, poria cocos 10 - 12 parts, ground beetle 6 - 9 parts, paris polyphylla 6 - 9 parts, notoginseng powder 3 - 6 parts.

[0009] Further, the traditional Chinese medicine composition is made from the following raw materials in parts by mass: Astragalus membranaceus 30 parts, Chinese cinnamon twig 10 parts, angelica sinensis 12 parts, stir-fried peach kernels 10 parts, rheum officinale 6 parts, poria cocos 10 parts, ground beetle 9 parts, paris polyphylla 9 parts, notoginseng powder 3 parts.

[0010] In the second aspect of the present invention, there is provided a preparation method of the above traditional Chinese medicine composition, and the method includes but is not limited to water decoction method, water extraction and alcohol precipitation method, enzymatic hydrolysis method, acid-base extraction method and ultrasonic extraction method, and preferably the water decoction method.

[0011] In the third aspect of the present invention, there is provided the application of the above traditional Chinese medicine composition in the preparation of a pharmaceutical preparation for preventing and / or treating adenomyosis with yang deficiency and blood stasis type.

[0012] In a fourth aspect, the present invention provides a pharmaceutical preparation for the prevention and / or treatment of adenomyosis of the Yang deficiency and blood stasis type, the pharmaceutical preparation comprising at least the above-mentioned traditional Chinese medicine composition; further, the pharmaceutical preparation may also comprise pharmaceutically acceptable excipients.

[0013] Compared with the prior art, the technical solution of the present invention has the following beneficial effects: The traditional Chinese medicine composition provided by the above-mentioned technical solution has been clinically proven to significantly alleviate dysmenorrhea and chronic pelvic pain, and significantly improve menorrhagia and prolonged menstrual periods, with a significant reduction in TCM syndrome scores. The efficacy remained stable over a 3-menstrual cycle follow-up period. It also effectively increases hemoglobin levels, improves anemia, and addresses the clinical challenge of anemia secondary to adenomyosis. Furthermore, no drug-induced damage was observed in blood, urine, and liver and kidney function tests before and after medication, and vital signs such as body temperature, pulse, respiration, and blood pressure showed no significant fluctuations. No significant adverse reactions occurred during medication. Animal experiments showed that the traditional Chinese medicine composition provided by the above-mentioned technical solution can improve the uterine morphology and structure in adenomyosis model mice, inhibit lesion invasion and growth, and has no toxicity to the liver and kidney function of mice, thus demonstrating good safety. Moreover, this application is specifically targeted at patients with adenomyosis of the Yang deficiency and blood stasis type, covering common clinical syndromes, and is applicable to a wide range of people, facilitating clinical promotion and application. Attached Figure Description

[0014] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0015] Figure 1 The images show the morphological structure of mouse uterine tissue; where A is the blank group, B is the model group, C is the traditional Chinese medicine group of this invention, D is the Tongmai Huazheng compound group, and E is the mifepristone group.

[0016] Figure 2 The morphological structure of mouse liver, spleen, and kidney tissues.

[0017] Figure 3 The images show HE staining of mouse uterus; where A is the blank group, B is the model group, C is the traditional Chinese medicine group of this invention, D is the Tongmai Huazheng compound group, and E is the mifepristone group.

[0018] Figure 4 The activities of AST (A), ALT (B), ALP (C) and BUN (D) in the peripheral blood of mice in each experimental group were measured. Detailed Implementation

[0019] It should be noted that the following detailed descriptions are exemplary and intended to provide further illustration of the invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0020] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments of the present invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, and / or combinations thereof.

[0021] In a typical embodiment of the present invention, a traditional Chinese medicine composition for treating adenomyosis is provided, said composition being made from the following raw materials in parts by weight: Astragalus membranaceus 20-45 parts, Cinnamomum cassia 10-15 parts, Angelica sinensis 10-15 parts, stir-fried peach kernel 10-15 parts, rhubarb (processed with wine) 6-9 parts, Poria cocos 10-12 parts, Eupolyphaga sinensis 6-9 parts, Paris polyphylla 6-9 parts, Panax notoginseng powder 3-6 parts.

[0022] Furthermore, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 30 parts Astragalus membranaceus, 10 parts Cinnamomum cassia, 12 parts Angelica sinensis, 10 parts stir-fried Prunus persica, 6 parts Rheum palmatum (processed with wine), 10 parts Poria cocos, 9 parts Eupolyphaga sinensis, 9 parts Paris polyphylla, and 3 parts Panax notoginseng powder.

[0023] It should be noted that the above-mentioned raw materials can be traditional Chinese medicine decoction pieces; at the same time, for the convenience of drug quality control, the above-mentioned raw materials can also be Chinese medicine formula granules made by extracting and concentrating Chinese medicine decoction pieces according to traditional standards, without specific limitations.

[0024] The herbal composition of this invention belongs to the category of traditional Chinese medicine prescriptions, and its rationale is as follows: The two principal herbs are Astragalus membranaceus and Cinnamomum cassia. Cinnamomum cassia is pungent and sweet in taste, and warm in nature. It warms and unblocks the blood vessels and assists Yang in transforming Qi. Astragalus membranaceus is sweet in taste and slightly warm in nature. It strengthens the spleen and replenishes the middle Jiao, invigorates Qi and raises Yang, and generates fluids and nourishes blood. In this invention, the dosage of Astragalus membranaceus is increased to enhance its effect of invigorating Yang and warming Yang, which, combined with the principle of using Astragalus membranaceus as the principal herb in Buyang Huanwu Decoction to invigorate Qi and unblock the blood vessels, is the purpose of this formula. The two herbs are combined as the principal herbs to warm and unblock Yang Qi, invigorate blood and unblock the blood vessels, and govern the entire formula.

[0025] The three auxiliary herbs are Angelica sinensis, stir-fried peach kernel, and rhubarb processed with wine. Angelica sinensis is pungent and sweet in taste, and warm in nature. It nourishes blood, invigorates blood circulation, regulates menstruation, and relieves pain. Combined with the principal herb Astragalus membranaceus, it tonifies qi and nourishes blood, and removes blood stasis, embodying the principle of "Angelica sinensis blood-nourishing decoction." Stir-fried peach kernel has a slightly fragrant aroma and a slightly bitter taste. It is neutral in nature and has the effect of invigorating blood circulation and removing blood stasis. When used with the principal herb Cinnamomum cassia, it can enhance the warming and invigorating effects of blood circulation. Rhubarb processed with wine is bitter in taste and cold in nature. After being processed with wine, its properties become even milder, its purgative effect is reduced, and its ability to eliminate stagnation and remove blood stasis is enhanced.

[0026] The four auxiliary herbs are Poria cocos, Eupolyphaga sinensis, Paris polyphylla, and Panax notoginseng powder. Poria cocos is sweet and bland in taste, and neutral in nature. It strengthens the spleen, resolves phlegm, and promotes diuresis. Combined with Cinnamomum cassia, it helps to regulate the middle yang, transform qi, and unblock the meridians. Together with the principal herb Cinnamomum cassia and the assistant herb roasted peach kernel, it derives from the "Cinnamomum cassia and Poria cocos pill" formula in the *Synopsis of Prescriptions of the Golden Chamber*. This is the first recorded formula in ancient Chinese medicine for treating abdominal masses in gynecology. The improved formula emphasizes promoting yang, activating blood circulation, and promoting diuresis, treating both blood and fluid retention, and gradually eliminating abdominal masses. Eupolyphaga sinensis is salty and cold in nature. It is adept at moving and has the function of breaking up blood stasis, eliminating masses, and dispersing nodules. The ground beetle (Eupolyphaga sinensis) gently attacks internal blood stasis. Combined with rhubarb (processed with wine), it effectively clears blood stasis in the lower abdomen. These two herbs, along with stir-fried peach kernel, form the "Blood Stasis Removal Decoction" in the *Synopsis of Prescriptions of the Golden Chamber*, which functions to break up blood stasis and treat "dry blood in the abdomen," enhancing the overall formula's ability to invigorate blood, remove blood stasis, and relieve pain. Paris polyphylla (Paris polyphylla), bitter, pungent, and slightly cold, has the effects of invigorating blood, stopping bleeding, reducing swelling, and detoxifying. Panax notoginseng powder, warm in nature, sweet and slightly bitter in taste, functions to stop bleeding, disperse blood stasis, and relieve pain. These four adjuvant herbs focus on resolving blood stasis, stopping bleeding, and relieving pain, directly targeting the two core symptoms of adenomyosis: bleeding and pain. Furthermore, Paris polyphylla is the only ingredient in the traditional Chinese medicine Gongxue Ning Capsules, used to treat gynecological bleeding disorders. Modern pharmacology has confirmed its anti-tumor effects. Because adenomyosis patients often develop blood stasis and toxicity, a small amount of Paris polyphylla is added to achieve the effects of detoxification, dispersing stagnation, resolving blood stasis, and relieving pain.

[0027] The formula contains nine herbs. Five of them—cinnamon twig, angelica root, astragalus root, poria cocos, and notoginseng powder—are warm in nature and sweet in taste. Cinnamon twig, the principal herb, is also pungent. Based on the principle in the *Huangdi Neijing* that "pungent and sweet herbs disperse and generate yang," it warms and invigorates yang qi and harmonizes qi and blood. The remaining four herbs—fried peach kernel, ground beetle, wine-processed rhubarb, and Paris polyphylla—are salty, bitter, and cold in nature, and are used to soften hardness and purge, thus resolving blood stasis and eliminating masses. Together, these herbs warm yang, resolve blood stasis, and eliminate masses, making it suitable for treating various symptoms of adenomyosis due to yang deficiency and blood stasis.

[0028] This drug combination is an optimized version of the "Tongmai Huazheng Compound" (hereinafter referred to as "the Compound"), a clinically proven formula developed by the inventor. The differences between this invention and the original Compound are as follows: This invention is a Compound without Chuanxiong, Chishao, Mudanpi, and Baihuasheshecao, and with the addition of Sanqi powder. Chuanxiong is pungent and warm in nature, with strong dispersing power. It is a qi-regulating herb in the blood and is often combined with Danggui. However, there is already Guizhi, a pungent herb, which is better at warming and unblocking the blood vessels. There are also blood-activating herbs such as Danggui and Taoren. Therefore, these herbs were appropriately removed in this invention. This is because this invention treats adenomyosis by focusing more on warming yang, tonifying qi, and resolving blood stasis rather than promoting qi circulation and resolving blood stasis. Red peony root and peony bark, while promoting blood circulation and removing blood stasis, tend to clear heat and cool the blood, and have the effect of nourishing blood and astringing yin. However, this invention optimizes and reduces the red peony root and peony bark, which tend to clear heat and cool the blood, among the blood-activating and stasis-removing herbs. Considering that the properties of herbs such as Paris polyphylla and rhubarb are cold, the whole formula is now balanced in terms of cold and warm properties. The original compound composition included cinnamon twig, poria cocos, roasted peach kernel, peony bark, and red peony root, which is the complete composition of Guizhi Fuling Wan. After optimization, the principal herb Guizhi, the assistant herb Peach Kernel, and the adjuvant herb Poria cocos are still retained in Guizhi Fuling Wan. Oldenlandia diffusa is cold in nature and has the functions of clearing heat and detoxifying, and activating blood circulation. It focuses on attacking the blood stasis caused by "heat, toxin, and dampness" evils, which is similar to the effect of Paris polyphylla. Both also have anti-tumor effects, so it is appropriately reduced. However, when using the compound in clinical practice to treat menorrhagia and abnormal bleeding outside of menstruation caused by adenomyosis, the hemostatic effect is not satisfactory. Therefore, this invention adds Panax notoginseng powder as appropriate, which can not only promote blood circulation, remove blood stasis and relieve pain, but also remove blood stasis and stop bleeding, thus enhancing the hemostatic effect of this invention.

[0029] In another specific embodiment of the present invention, a method for preparing the above-mentioned traditional Chinese medicine composition is provided, the method including but not limited to water decoction, water extraction and alcohol precipitation, enzymatic hydrolysis, acid-base extraction and ultrasonic extraction, preferably water decoction.

[0030] In another specific embodiment of the present invention, the application of the above-mentioned traditional Chinese medicine composition in the preparation of pharmaceutical preparations for the prevention and / or treatment of adenomyosis of the Yang deficiency and blood stasis type is provided.

[0031] In another specific embodiment of the present invention, a pharmaceutical preparation for preventing and / or treating adenomyosis of the Yang deficiency and blood stasis type is provided, wherein the pharmaceutical preparation contains at least the above-mentioned traditional Chinese medicine composition as a pharmaceutical active ingredient.

[0032] Specifically, in addition to the aforementioned active pharmaceutical ingredients, the traditional Chinese medicine preparation may also contain pharmaceutically acceptable excipients and / or carriers. The content of the excipients and / or carriers in the traditional Chinese medicine preparation may be 1% by weight to 98% by weight, including but not limited to 5% by weight, 10% by weight, 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight, 95% by weight, and 98% by weight, typically approximately 80% by weight.

[0033] The pharmaceutical preparation can be formulated into various dosage forms, preferably oral liquids, decoctions, pills, capsules, tablets, powders or granules, etc., which are suitable for practical applications.

[0034] In another specific embodiment of the present invention, the pharmaceutically acceptable excipients in the pharmaceutical preparation include, but are not limited to, one or more of the following: diluents, fillers, disintegrants, lubricants, binders, flow agents, complexing agents, plasticizers, colorants, sweeteners, viscosity enhancers, preservatives, or antioxidants.

[0035] In another specific embodiment of the present invention, the diluent includes, but is not limited to, sorbitol, mannitol, starch, lactose, powdered or microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, etc. The fillers include, but are not limited to, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, gelatinized starch, etc. The disintegrants include, but are not limited to, dry starch, crospovidone, crospovidone sodium carboxymethyl cellulose, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose. The lubricant includes, but is not limited to, magnesium stearate, sodium dodecyl sulfate, or micronized silica gel.

[0036] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0037] Example I. Clinical Research 1. Materials and Methods Inclusion criteria: ① Patients who meet the Western medicine diagnostic criteria for adenomyosis and the traditional Chinese medicine diagnostic criteria for Yang deficiency and blood stasis syndrome, and whose main symptoms are dysmenorrhea, menorrhagia, and chronic pelvic pain; ② Patients aged 18 to 49 years who have not gone through menopause; ③ Patients who voluntarily and informedly participate in the clinical study.

[0038] Exclusion criteria: ① Use of hormone medications within the past three months; ② Comorbid fibroids or endometriomas ≥5cm; ③ Hemoglobin <90g / L; ④ Comorbid severe cardiovascular and cerebrovascular complications; ⑤ Abnormal liver and kidney function; ⑥ Pregnant and lactating women.

[0039] 2. Medication regimen: (1) The ingredients of this invention are: Astragalus membranaceus 30g, Cinnamomum cassia 10g, Angelica sinensis 12g, stir-fried Prunus persica 10g, Rheum palmatum 6g, Poria cocos 10g, Eupolyphaga sinensis 9g, Paris polyphylla 9g, Panax notoginseng powder 3g (to be taken separately). Each dose is decocted to 400ml, and 200ml is taken warm half an hour after breakfast and dinner. One dose is taken daily outside of menstruation for a cumulative period of 20 days.

[0040] (2) Tongmai Huazheng Mixture Group: Take 50ml twice a day, half an hour after breakfast and dinner. Take continuously for 20 days outside of menstruation.

[0041] (3) Dydrogesterone tablets: take one tablet twice a day, starting from the 6th day of menstruation, for 20 consecutive days.

[0042] Treatment course: The medication is taken for three menstrual cycles, followed by a three-month follow-up observation.

[0043] 3. Observation Indicators (1) Dysmenorrhea VAS score; (2) Menstrual blood loss graph PBAC score; (3) Chronic pelvic inflammatory disease CPP score; (4) Uterine volume under intracavitary gynecological color Doppler ultrasound; (5) Serum CA125; (6) Hemoglobin; (7) Traditional Chinese medicine syndrome score.

[0044] Statistical methods: Statistical analysis was performed using SPSS 27.0 software. Normally distributed continuous data were expressed as mean ± standard deviation, and non-normally distributed data were expressed as median (interquartile range). For comparisons within a group at different time points, repeated measures ANOVA (Greenhouse-Geisser corrected) was used for normally distributed data, and Friedman's test was used for non-normally distributed data. Pairwise comparisons were corrected for Bonferroni. Between-group comparisons were performed using independent samples t-tests or Mann-Whitney U tests. The significance level was set at α = 0.05, and p < 0.05 was considered statistically significant.

[0045] 5. Research Results: (1) Basic information: A total of 30 cases were included. The average age was (39.2±3.03) years.

[0046] (2) The overall clinical efficacy is shown in Table 1.

[0047] Table 1 Overall Clinical Efficacy

[0048] Overall effectiveness rate = (Significantly effective + Effective) / Total number of cases × 100% Significant effect: refers to complete or significant relief of symptoms. For example, a significant decrease in VAS score, reduced menstrual flow, and relief of chronic pelvic pain.

[0049] Effective: This means that symptoms have improved, but may not have completely disappeared. For example, the VAS score may have decreased, but the improvement is small.

[0050] Ineffective: This means that the symptoms have not improved significantly, or that the symptoms have not improved after treatment, or may even have worsened.

[0051] (3) The changes in VAS scores are shown in Table 2.

[0052] Table 2 VAS Scores

[0053] Analysis: ① Treatment efficacy within the group: VAS scores in both groups were significantly lower after treatment than before treatment (both P < 0.05), indicating that both interventions can effectively improve pain, and the efficacy can be maintained until the follow-up stage. At each follow-up time point, compared with after treatment, the scores did not show significant rebound or further significant decrease, indicating stable treatment efficacy.

[0054] ② Differences in efficacy between groups: There was no statistically significant difference in baseline VAS levels between the two groups before treatment (P>0.05); after treatment and at each follow-up time point, the VAS scores between the two groups were all compared (P>0.05), indicating that there was no significant difference in the degree of pain improvement between the two groups.

[0055] ③ Overall trend: The VAS scores of both groups showed a downward trend followed by a stabilization trend, and the values ​​remained at a low level, indicating that both treatments can effectively and continuously relieve pain, and the fluctuations were stable during the follow-up period, with comparable efficacy between the two groups.

[0056] (4) The changes in PBAC scores are shown in Table 3.

[0057] Table 3. Comparison of PBAC scores before and after treatment (±s)

[0058] Analysis: ① Intra-group comparison: The optimized formula showed a significant decrease in indicators after treatment compared to before treatment (P < 0.001), and the values ​​remained at a low level at all three follow-up time points from treatment onwards, without significant rebound, and the differences were not statistically significant, suggesting that the intervention effect was stable and durable. The compound preparation group showed a significant decrease in indicators after treatment compared to before treatment (P < 0.001), but the indicators gradually rebounded from follow-up 1 to follow-up 3, and the differences compared to after treatment were statistically significant, suggesting short-term effectiveness, but the long-term efficacy gradually diminishes.

[0059] ② Intergroup comparison: There was no statistically significant difference in baseline levels between the two groups before treatment (P>0.05); after treatment and at each follow-up time point, the indicators of the optimized formula group were significantly better than those of the compound preparation group (all P<0.001), suggesting that the intervention of the optimized formula group was significantly better than that of the compound preparation group in reducing indicators and maintaining long-term efficacy.

[0060] ③ Overall trend: After intervention with the optimized formula, the level remained low, and the long-term effect was stable; the compound was only effective in the short term, and the indicators rebounded significantly over time, with significant differences in the long-term efficacy between the two groups.

[0061] (5) The comparison of TCM syndrome efficacy is shown in Table 4.

[0062] Table 4. Traditional Chinese Medicine Syndrome Scoring Table

[0063] Analysis: ① Intra-group comparison: The TCM score of the optimized formula was significantly lower after treatment than before treatment (P<0.001). At follow-up 1 and 2, the score did not show a significant rebound compared to after treatment, and the difference was not statistically significant. At follow-up 3, the score slightly increased but was still significantly improved compared to before treatment, indicating significant short-term efficacy with good maintenance. The score of the compound preparation group was significantly lower after treatment than before treatment (P<0.001), but the score gradually rebounded at follow-up 1–3, and the difference compared to after treatment was statistically significant, suggesting only short-term effectiveness, with long-term efficacy gradually diminishing.

[0064] ② Intergroup comparison: There was a statistically significant difference in VAS scores between the two groups before treatment (P=0.012), and the baselines were not comparable; after treatment, the differences between the two groups were close to statistically significant (P=0.079), and at follow-up 1, the score of the optimized formula group was significantly lower than that of the compound formula group (P=0.006); at follow-up 2 and 3, there was no statistically significant difference between the two groups, but at follow-up 1, the score of the optimized formula group was still lower than that of the compound formula group overall.

[0065] ③ Overall trend: Both interventions can improve scores in the short term, but the optimized formula group has more stable efficacy and milder long-term rebound, and is better than the compound formula group overall.

[0066] (6) The chronic pelvic CPP score is shown in Table 5.

[0067] Table 5 Chronic Pelvic CPP Score

[0068] Analysis: ① Intra-group comparison: In the optimized formula group, CPP was significantly lower after treatment than before treatment (P<0.001); at follow-up 1, it slightly rebounded but remained better than before treatment (P<0.05); at follow-up 2 and 3, it tended to stabilize, with no statistically significant difference from the post-treatment level, suggesting that the intervention was effective and the efficacy could be maintained relatively well. In the compound preparation group, CPP was significantly lower after treatment than before treatment (P<0.001), but it rebounded significantly at follow-up 1, and at follow-up 2 and 3, it basically returned to the pre-treatment level, suggesting that it was only effective in the short term, and the long-term efficacy was significantly reduced.

[0069] ② Intergroup comparison: There was no statistically significant difference in baseline CPP levels between the two groups before treatment (P>0.05); after treatment and at follow-up 1, the CPP of the optimized formula group was significantly better than that of the compound formula group (both P<0.01); at follow-up 2 and 3, there was no statistically significant difference between the two groups, but the overall indicators of the optimized formula group were still better than those of the compound formula group.

[0070] ③ Overall conclusion: Both interventions can reduce CPP levels in the short term. The optimized group showed more stable long-term efficacy, milder rebound, and significantly better overall improvement than the compound preparation.

[0071] (7) The volume of the uterus under intracavitary gynecological ultrasound is shown in Table 6.

[0072] Table 6. Uterine volume (cm²) as seen on endoscopic gynecological ultrasound. 3 )

[0073] Analysis: ① Intra-group comparison: There were no statistically significant differences in uterine volume between the two groups before and after treatment and at each follow-up time point, indicating that the intervention measures in both groups did not have a significant effect on uterine volume.

[0074] ② Intergroup comparison: Before treatment, there was no statistically significant difference in the baseline uterine volume between the two groups (P=0.178), making them comparable; after treatment and at follow-up 1, the uterine volume in the compound preparation group was significantly smaller than that in the optimized formula group (P=0.033, P=0.010); at follow-up 2, there was no statistically significant difference between the two groups (P=0.724); at follow-up 3, the difference between the two groups was close to statistically significant (P=0.085), and overall, the uterine volume in the compound preparation group was still relatively smaller.

[0075] ③ Overall conclusion: Neither intervention method significantly improved uterine volume; in the intergroup comparison, the uterine volume of the two-drug group was smaller than that of the optimized formula group, but the difference did not show a sustained and stable statistical significance.

[0076] (8) Hemoglobin expression levels are shown in Table 7.

[0077] Table 7 Hemoglobin Expression Levels (g / L)

[0078] Analysis: ① Within-group comparisons: The main effect of measurement time points in the optimized formula group (F=11.794) was statistically significant (P<0.001), indicating that hemoglobin levels showed a significant increasing trend with the treatment process, mainly with linear increase and quadratic curve changes (all P<0.01). Bonferroni pairwise comparisons showed that hemoglobin levels after treatment were significantly higher than before treatment (P<0.05); levels at follow-up 1, follow-up 2, and follow-up 3 were consistently significantly higher than before treatment (all P<0.05). There were no statistically significant differences between follow-up time points (all P>0.05), suggesting that hemoglobin levels gradually increased after treatment and remained at a stable high level during the follow-up period. Repeated measures ANOVA (Greenhouse-Geisser corrected) in the combination therapy group showed no statistically significant main effect of measurement time (P>0.05). Pairwise comparisons by Bonferroni showed no statistically significant differences in hemoglobin levels after treatment and at each follow-up time point compared to before treatment (all P>0.05), and no statistically significant differences were found between each follow-up time point. This suggests that hemoglobin levels remained stable throughout the observation period without significant improvement.

[0079] ② Intergroup comparison: From the start of treatment to follow-up 1, the hemoglobin level in the optimized formula group showed an increasing trend compared to the compound preparation group, but the difference was not statistically significant. From follow-up 2 onwards, the hemoglobin level in the optimized formula group was significantly higher than that in the compound preparation group, and the difference further widened at follow-up 3, suggesting that the optimized formula group had a more significant and longer-lasting effect in increasing hemoglobin, and its long-term efficacy was superior to that of the compound preparation.

[0080] (9) The expression level of CA125 is shown in Table 8.

[0081] Table 8. CA125 expression levels (U / mL)

[0082] Analysis: ① Intra-group comparison: After treatment with the optimized formula, CA125 significantly decreased compared to before treatment (P=0.027); at follow-up 2 and 3, it further decreased, both significantly better than before treatment (both P<0.05); there was no statistically significant difference at follow-up 1 compared to before treatment (P>0.05); there were no statistically significant differences between the post-treatment and follow-up points. In the compound preparation group, after treatment, CA125 significantly decreased compared to before treatment (P=0.018); at follow-up 2 and 3, it continued to decrease, both significantly better than before treatment (both P<0.05); there was no statistically significant difference at follow-up 1 compared to before treatment (P>0.05); there were no statistically significant differences between the post-treatment and follow-up points. Both groups showed a short-term decrease after treatment, with the level remaining at a low level in the medium to long term.

[0083] ② Intergroup comparison: There were no statistically significant differences in CA125 levels between the two groups before treatment, after treatment, during follow-up 1, follow-up 2, and follow-up 3 (all P > 0.05).

[0084] ③ Overall conclusion: Both intervention methods can significantly reduce CA125 levels, and the efficacy can be maintained stably until follow-up 3; in terms of reducing CA125, the two groups have comparable effects and no significant difference was shown.

[0085] (10) Safety Evaluation: Blood, urine, and liver and kidney function tests before and after taking this invention showed no drug-induced damage, and body temperature, pulse, respiration, heart rate, and blood pressure showed no significant fluctuations, indicating that the drug does not damage the liver and kidney function of the human body, and no obvious adverse reactions occurred during the medication period. The above experimental studies show that after optimization and improvement, the traditional Chinese medicine composition of this invention has significant effects, significantly relieving pain such as dysmenorrhea and chronic pelvic pain, while also having a better effect on improving menorrhagia and hemoglobin levels.

[0086] II. Animal Experimental Research Experimental drugs: ① The herbal composition of this invention: Astragalus membranaceus 30g, Cinnamomum cassia twig 10g, Angelica sinensis 12g, stir-fried peach kernel 10g, rhubarb (processed with wine) 6g, Poria cocos 10g, Eupolyphaga sinensis 9g, Paris polyphylla 9g, Panax notoginseng powder 3g, water extract, administered by gavage at 36.51 g / kg, once daily. ② The combination of blood-activating and stasis-resolving agents: Cinnamomum cassia twig 10g, Angelica sinensis 10g, raw Astragalus membranaceus 20g, Poria cocos 10g, Ligusticum chuanxiong 9g, Paeonia lactiflora 10g, Paeonia suffruticosa 10g, stir-fried peach kernel 10g, Eupolyphaga sinensis 9g, rhubarb (processed with wine) 6g, Paris polyphylla 9g, Hedyotis diffusa 10g. ③ Mifepristone group: administered by gavage at 3.25 mg / kg mifepristone.

[0087] Experimental animals and model establishment: ICR mice. The tamoxifen model was established according to the literature "Shi Yaxin, Wang Zilu, Cao Han, et al. Molecular mechanism of Paris saponin VII inhibiting the migration and invasion of ectopic endometrium in adenomyosis by regulating epithelial-mesenchymal transition [J]. Chinese Journal of Traditional Chinese Medicine, 2024, 39(05):2534-2541." HE staining pathological reading showed disordered endometrial structure and invasion of endometrial glandular cells and stromal cells into the myometrium, proving that the model was successful.

[0088] Grouping and administration: ① Blank group; ② Model group; ③ Traditional Chinese medicine group of this invention; ④ Tongmai Huazheng compound group; ⑤ Mifepristone group.

[0089] Testing indicators: (1) Observation of tissue morphology: Take tissues of uterus, liver, spleen and kidney of mice in each group, observe the changes in tissue morphology and take pictures to record.

[0090] (2) HE staining: Mouse uterus was fixed with 4% paraformaldehyde, embedded in paraffin, and sectioned. The sections were dewaxed in xylene, stained with hematoxylin for 20 seconds, counterstained with eosin for 30 seconds, and then rinsed with water to complete the dehydration and clearing process. The sections were then mounted with mounting medium and finally photographed under a pathological slide scanner. Histological observation: Uterus, liver, spleen, and kidney tissues of mice in each group were taken, and the changes in histological morphology were observed and photographed.

[0091] (3) ELISA method to detect the activities of AST, ALT, ALP and BUN in peripheral blood of mice: Blood was collected from each group of mice by enucleation using a coagulation tube, allowed to stand at room temperature for 30 min, centrifuged at 3200 r / min for 15 min, and the supernatant was collected. The activities of AST, ALT, ALP and BUN in serum were detected according to the ELISA kit instructions.

[0092] The results show that the herbal combination of the present invention can improve the uterine morphology and structure of mice with adenomyosis, inhibit the invasion and growth of lesions into the myometrium, and has no liver or kidney toxicity.

[0093] III. Typical Cases Case 1: Ms. Li, 37 years old. First visit in early April 2022.

[0094] Chief complaint: Right lower abdominal pain for more than 10 months, and adenomyosis diagnosed six months ago.

[0095] Medical History: Last June, the patient experienced significant emotional fluctuations followed by lower right abdominal pain for about two weeks after her period ended. The pain worsened every night before bed, affecting her sleep. On November 1, 2021, a gynecological ultrasound at a provincial tertiary hospital showed: 1. Adenomyosis (observation), 2. Uterine fibroids (observation), 3. Right ovarian cyst, and 4. Small amount of pelvic fluid. She was diagnosed with adenomyosis and treated with dinogest for 5 months, which slightly improved her lower abdominal pain. On January 19, 2022, a follow-up gynecological ultrasound showed: 1. Sonographic image of adenomyosis; 2. Uterine fibroids; 3. PCO (progressive ovarian cancer) to be ruled out. She continues taking dinogest. She is currently trying to conceive. She typically experiences fatigue, weakness, and cold intolerance, has a good appetite, poor sleep, and regular bowel movements.

[0096] Menstrual history: Menarche at age 13, 7 / 30 days. After childbirth, menstrual periods shortened to 3 days, with normal flow, bright red color, and dark blood clots, accompanied by menstrual cramps and cold intolerance. No menstruation since taking dinogest last November. LMP: October 14, 2021, lasted 3 days, other details same as before.

[0097] Marital and reproductive history: Married, G2P2L1A0, two vaginal births. One daughter passed away due to illness, and one son is healthy.

[0098] Tongue and pulse: The tongue is dark red with a thin white coating and slight teeth marks on the edges; the sublingual veins are clearly varicose; the pulse is slow and deep.

[0099] Gynecological examination: Vulva: past delivery; Vagina: patent, with a small amount of discharge; Cervix: smooth, no bleeding upon touch; Uterus: retroverted, about the size of a 50-day pregnancy, no tenderness or motion pain; Adnexa: no abnormalities found in either adnexa.

[0100] Diagnosis: Traditional Chinese Medicine diagnosis: 1. Dysmenorrhea 2. Abdominal masses due to spleen and kidney yang deficiency and blood stasis. Western Medicine diagnosis: Adenomyosis.

[0101] Treatment principle: Warm the Yang, remove blood stasis, and eliminate masses.

[0102] Treatment plan: Discontinue dinogest and take the herbal composition (decoction) of the present invention for 3 months.

[0103] Follow-up: Menstruation resumed, with a cycle of 28-30 days, a menstrual period of 4-6 days, and acceptable flow, color, and consistency. Dysmenorrhea gradually improved, right lower abdominal pain significantly improved, and sleep improved. Medication was continued for 3 months without fatigue or cold intolerance. Medication was discontinued on the patient's own after more than six months of use. The following month, delayed menstruation occurred occasionally, and a self-test for urine HCG was positive. One year of follow-up resulted in a vaginal delivery of a daughter.

[0104] Case 2: Wang, female, 40 years old. First visit in early January 2023.

[0105] Chief complaint: Menstrual cramps for 2 years, worsening in the past 6 months.

[0106] Medical History: Regular menstruation, lower abdominal pain on the first day of menstruation, relieved by warmth, which has worsened in the past six months; dysmenorrhea requiring ibuprofen for pain relief in the last three periods; slightly heavy menstrual flow, bright red color, with many blood clots. No systematic medical treatment has been received. Gynecological Ultrasound: 1. Adenomyosis 2. Pelvic effusion. Blood Routine: Hemoglobin: 109 g / L. No significant discomfort usually, good appetite and sleep, regular bowel movements.

[0107] Menstrual history: Menarche at age 12. 5-7 / 27-31 days, other details as above. LMP: 2023-1-7, lasted 6 days, dysmenorrhea, cold extremities, improved after taking 1 ibuprofen sustained-release capsule and resting in bed.

[0108] Marital and reproductive history: Married, G4P1L1A3, 1 cesarean section, 3 abortions.

[0109] Tongue and pulse: Dark red, with a thin white coating; dark purple veins under the tongue; deep and slow pulse.

[0110] Gynecological examination: Vulva: past delivery; Vagina: patent; Cervix: smooth, no bleeding upon touch; Uterus: anteverted, about the size of a 60-day pregnancy, firm in texture, no tenderness or motion pain; Adnexa: no abnormalities found in either adnexa.

[0111] Diagnosis: Traditional Chinese Medicine diagnosis: Dysmenorrhea due to Yang deficiency and blood stasis. Western Medicine diagnosis: 1. Adenomyosis 2. Mild anemia.

[0112] Treatment principle: Warm the Yang, remove blood stasis, and eliminate masses.

[0113] Treatment plan: Take the traditional Chinese medicine composition (decoction) of the present invention for 3 months.

[0114] Follow-up: Menstrual cramps were tolerable, and ibuprofen was not needed for pain relief. Medication was continued for one month; menstrual flow was normal, blood clots were significantly reduced, and there was no significant dysmenorrhea or cold intolerance during menstruation. Six-month follow-up showed no recurrence of dysmenorrhea, and hemoglobin levels returned to normal.

[0115] Case 3: Ms. Chen, 33 years old. First visit in early November 2021.

[0116] Chief complaint: Heavy menstrual bleeding for one year.

[0117] Medical History: Regular menstruation, lasting 7 days, with heavy flow for the first 5 days. Averages 6-7 night towels used daily, and one pair of overnight underwear, 2 / 3 full or completely soaked, with blood clots. Lower abdominal pain on the first day of menstruation, relieved by warmth. Previously took Yuanhu analgesics, with limited effect; occasionally needs ibuprofen for pain relief. Recent monthly physical examination at work: Blood routine: Hemoglobin: 99g / L; Gynecological ultrasound: 1. Adenomyosis 2. Uterine scar diverticulum. Usually fatigued, noticeably more sensitive to cold after autumn. Bowel movements and urination are normal.

[0118] Menstrual history: Menarche at age 13, 7-8 / 28-31 days, LMP: 2021.11.05, menstrual flow increased compared to the previous period, with blood clots, lower abdominal cold pain, took one ibuprofen tablet for pain relief.

[0119] Marital and reproductive history: G2P1L1A1, 1 medical abortion, 1 cesarean section.

[0120] Tongue and pulse: The tongue is dark, with a thin white coating and teeth marks on the edges; the sublingual veins are purplish-dark; the pulse is deep and slow.

[0121] Gynecological examination: Vulva: Paroxysmal position; Vagina: Patent; Cervix: Smooth, no bleeding upon touch; Uterus: Anteverted, about the size of a 50-day pregnancy, firm in texture, mobile, no tenderness or motion pain; Adnexa: No abnormalities found in either adnexa.

[0122] Diagnosis: Traditional Chinese Medicine diagnosis: Dysmenorrhea due to Yang deficiency and blood stasis. Western Medicine diagnosis: 1. Adenomyosis 2. Menorrhagia 3. Mild anemia.

[0123] Treatment principle: Warm the Yang, remove blood stasis, and eliminate masses.

[0124] Treatment plan: Take the traditional Chinese medicine composition (decoction) of the present invention for 3 months.

[0125] Follow-up: The first menstrual period after taking the medication lasted 8 days, with significantly fewer blood clots than before, and tolerable lower abdominal pain. The medication was continued for 3 months, during which menstruation lasted 6-7 days, with normal flow. For the first 3 days, 6-7 daytime pads and 1 nighttime pad were used. There was no dysmenorrhea, and all other symptoms improved. At the 6-month follow-up, menstrual flow remained within the normal range, with occasional tolerable lower abdominal pain; a hemoglobin test in May 2022 showed normal results.

[0126] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating adenomyosis, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: Astragalus membranaceus 20-45 parts, Cinnamomum cassia 10-15 parts, Angelica sinensis 10-15 parts, stir-fried peach kernel 10-15 parts, rhubarb (processed with wine) 6-9 parts, Poria cocos 10-12 parts, Eupolyphaga sinensis 6-9 parts, Paris polyphylla 6-9 parts, Panax notoginseng powder 3-6 parts.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: Astragalus membranaceus 30 parts, Cinnamomum cassia 10 parts, Angelica sinensis 12 parts, stir-fried peach kernel 10 parts, rhubarb (processed with wine) 6 parts, Poria cocos 10 parts, Eupolyphaga sinensis 9 parts, Paris polyphylla 9 parts, Panax notoginseng powder 3 parts.

3. The method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, The methods include water decoction, water extraction and alcohol precipitation, enzymatic hydrolysis, acid-base extraction, and ultrasonic extraction.

4. The preparation method according to claim 3, characterized in that, The method described is the water decoction method.

5. The use of the traditional Chinese medicine composition according to claim 1 or 2 in the preparation of pharmaceutical preparations for the prevention and / or treatment of adenomyosis of the Yang deficiency and blood stasis type.

6. A pharmaceutical preparation for the prevention and / or treatment of adenomyosis of the Yang deficiency and blood stasis type, characterized in that, The pharmaceutical preparation comprises at least the traditional Chinese medicine composition as described in claim 1 or 2; further, the pharmaceutical preparation may also comprise pharmaceutically acceptable excipients.

7. The pharmaceutical formulation according to claim 6, characterized in that, The pharmaceutical formulation contains pharmaceutically acceptable excipients and / or carriers.

8. The traditional Chinese medicine preparation as described in claim 7, characterized in that, The excipients and / or carriers constitute 1% to 98% by weight of the pharmaceutical formulation.

9. The traditional Chinese medicine preparation as described in claim 6, characterized in that, The dosage form of the drug preparation is either a liquid or a solid dosage form.

10. The traditional Chinese medicine preparation as described in claim 9, characterized in that, The liquid dosage forms include true solutions, colloids, microparticles, emulsions, and suspensions; The solid dosage forms include oral tablets and capsules.

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